1. Field of the Invention
The present invention relates to a dry analysis element having a constant blank value on a calibration curve, and process for making the dry analysis element. More particularly, the invention provides a dry analysis element which is conveniently used in an automated analyzer system having a fixed calibration curve, and also provides a process for preparing such a dry analysis element.
2. Prior Art Statement
Dry chemistry has been increasingly used in various clinical tests in recent years since they are easily handled and give results instantaneously. In order that the dry chemistries are handled more easily in a small-scale hospital by medical personnel, it is desirous that they can be used without the need of correction operation. This means that the test system need not be adjusted by using a standard solution or like control before it is used for practical test. An important merit of the systems in which dry chemistries are used is that a sample can be tested immediately at any desired time. In other words, a dry chemistry is used particularly conveniently when a small number of samples, sometimes a single sample, is subjected to test. By such a procedure, a real-time test result can be obtained to realize more effective medical treatment. However, need of correction operation obstructs a prompt test. If it is required to test individual samples promptly at any desired time, it becomes a problem when the correction operation of the system should be conducted or at what time intervals correction operations should be conducted. Since such a correction operation requires time and cost, need of correction operation poses a serious problem in case where the number of samples to be tested is so small as only one or two a day as is often a case in an individual doctor's office. Accordingly, if the correction operation becomes unnecessary, it contributes realization of effectual medical treatment at an extent more than that attainable by an improvement in prompt operation of the system. Although it is particularly preferable for the user if the correction operation of the system becomes not requisite, provision of such an analysis element imposes an extreme burden on the maker. This is because the analysis elements are usually produced by lots which are differentiated with each other due to the differences in used materials and variations of factors in the producing steps.
In automated analysis systems using dry chemistries which do not require daily correction operations, calibration curves are usually memorized in the analyzers per se. The calibration curves mean the graphs, numerical tables or equations indicating the interrelations between the quantities of individual analytes and the optical densities (hereinafter referred briefly to as "O.D.") of the coloring (including color changes and generation of fluorescent lights), and are usually obtained by the correction operations. In order to exempt the correction operation in a system in which a dry chemistry is used, the calibration curve must be obtained by the maker which is memorized in the analyzer. The thus memorized calibration curve will be referred to as internal calibration curve.
In order to guarantee the performance characteristics of a system in which an internal calibration curve is memorized, the characteristics of the available analysis elements shall not be shifted from the memorized internal calibration curve and the characteristics of the available analysis elements shall not be changed with the lapse of time. Non-shifting from the internal calibration curve means that the practical calibration curves of commercially available analysis elements are coincident with the memorized internal calibration curve. In general, properties of industrial products are dispersed and industrial standards are stipulated for individual products for standardization of industrial products. Likewise, coincidence of calibration curve means that the difference between the practical calibration curve and the memorized internal standard curve is within the standard allowable error range. Of course, the standard allowable error range must be narrow enough not to cause any problem in practice even if the properties of the products are changed within this range.
The calibration curves are linear in many cases, and can be represented by a linear equation of y=ax+b when the amounts (density, active value, activity, etc.) of analytes are plotted along the x-axis (abscissa) and the O.D. of coloring or like are plotted along the y-axis (ordinate). In the equation set forth above, slope a indicates the extent of changeability of O.D. in terms of the quantitity of the analyte to be analyzed, and thus a will be referred to as sensitivity constant. In the same equation, b indicates the blank value when the quantity of the analyte is zero, and thus b will be referred to as blank constant.
In the systems wherein dry chemistries are used, since the optical densities of reflected lights are usually measured, there are often cases where the obtained calibration curves are not linear. In such a case, the calibration curves may be transfigured into linear by transforming the same while making use of an interrelation between the reflected light and the transmitted light. However, rarely is a linear calibration curve obtained. It is considered that such a result is due to the fact that the total yield of the complicated reactions in the plural layer is not 100 percent. Even when the obtained calibration curve is a slightly arcuated curve, it may be deemed expediently as approximate to linear and expressed by the two parameters, i.e. the sensitivity constant a and the blank constant b. Particularly when the products are the same kinds, such an approximation is acceptable, since the curvature of the arcuated curve are identical if the structure of layers and the reaction mechanisms are identical.
The sensitivity constant a and the blank constant b are varied depending on the variations in processing steps and properties of the used raw materials. Particularly, the blank constant b is affected by the variation in properties of the used raw materials. If the blank constant is varied for every lot, the internal calibration curve must be altered for every lots or the internal calibration curve must be corrected using a standard solution, leading to the result that the merit of the dry chemistry is injured seriously.
In view of the above, it is desirous that the raw materials used for the preparation of analysis element should have constant purities, and preferably be as pure as possible. However, raw materials usually contain various impurities. Particularly, raw materials of natural origin or materials which tend to decompose to produce decomposition products during the preparation steps or storage time contain different quantities of impurities. Some examples of unstable raw materials will be set forth below.
(1) Since the bond gelatine forms a bone together with calcium (Ca), it contains Ca. When the bone gelatine is used as a raw material for the preparation of an analysis element for analyzing Ca, the blank constant b is affected significantly by the Ca contained as an impurity in the raw bone gelatine.
(2) Since diazonium salts used as the color formers are unstable, portions thereof are decomposed during the refining step to form dyes having absorption peaks within the visible range. Accordingly, when a diazonium salt is used for the preparation of an analysis element for analyzing bilirubin, the blank constant b is affected by the dye formed by decomposition of the diazonium salt.
(3) When a color former of redox system wherein hydrogen peroxide is used as an intermediate product is used, the blank constant b is sometimes affected by oxides contained in raw materials.
Since the blank constant b is varied by the above and other factors, it is desirous that the used raw materials are sufficiently refined to use at high purities in order to remain the blank constant at a constant value. However, purification of raw materials causes increase in cost, and when the raw materials are used without purifying them, the produced analysis element does not pass the quality control inspection so frequently as to lead an increase in cost of the acceptable product. There is, therefore, a demand for maintaining the blank constant b at a constant value without increasing the cost for preparing the raw materials.